Type

Other / n/a

Authors

Graham P Pidgeon
Kenneth J O'Byrne
Elaine Kay
Robert Cummins
Kathy Gately
Mary-Clare Cathcart

Subjects

Biochemistry

Topics
carcinoma non small cell lung blotting western cell line tumor tumor male medical pathology pathology gene expression regulation enzymologic lung neoplasms cyclooxygenase 2 prognosis immunohistochemistry gene expression regulation neoplastic western apoptosis blotting enzyme inhibitors non small cell lung cell proliferation cell line adenocarcinoma carcinoma humans enzymologic tissue array analysis gene expression regulation thromboxane a synthase thromboxane b2 neoplastic reverse transcriptase polymerase chain reaction female

Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer. (2011)

Abstract BACKGROUND: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease.METHODS: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression.RESULTS: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis.CONCLUSION: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
Collections Ireland -> Royal College of Surgeons in Ireland -> Pathology Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Pathology

Full list of authors on original publication

Graham P Pidgeon, Kenneth J O'Byrne, Elaine Kay, Robert Cummins, Kathy Gately, Mary-Clare Cathcart

Experts in our system

1
Graham Pidgeon
Trinity College Dublin
Total Publications: 38
 
2
Kenneth J O'Byrne
Trinity College Dublin
Total Publications: 37
 
3
Elaine W Kay
Royal College of Surgeons in Ireland
Total Publications: 157
 
4
Robert Cummins
Royal College of Surgeons in Ireland
Total Publications: 22
 
5
Kathy Gately
Trinity College Dublin
Total Publications: 22
 
6
Mary Clare Cathcart
Trinity College Dublin
Total Publications: 16